Melanomas and

Metastatic renal cell carcinoma has a poor prognosis and resists conventional chemotherapy. Immunotherapy with IL-2 and/or IFN-a is currently regarded as the most effective therapy with, however, modest response rates of 15-20%. Similar results are also observed in patients with metastatic melanoma and the response to IFN-a and IL-2 correlates with the occurrence of tumor-infiltrating CD4+ T-lymphocytes identified in aspirates from melanoma metastases. Determination of these cells therefore seems to be a method to predict responders prior to the initiation of cytokine therapy. 

Much attention has recently been focused on organoboronic acids and their esters because of their practical usefulness for synthetic organic reactions including asymmetric synthesis, combinatorial synthesis, and polymer synthesis [1, 3, 7-9], molecular recognition such as host-guest compounds [10], and neutron capture therapy in treatment of malignant melanoma and brain tumor ]11]. New synthetic procedures reviewed in this article wiU serve to find further appHcations of organoboron compounds. 

Identify the key features in the different stages of melanoma and their correlation with prognosis. 

Discuss the pros and cons of interferon-a therapy for melanoma, and formulate a monitoring plan for patients receiving interferon-a. 

Interleukin 2 therapy is approved by the Food and Drug Administration (FDA) for the treatment of metastatic melanoma, and it is a reasonable option for patients with this stage of the disease. 

Brain metastasis is common in melanoma, and treatment options for brain metastasis include surgery, radiation, and chemotherapy. The choice of therapy depends on the number of metastatic lesions, accessibility of the lesions for surgery, the presence of neurologic symptoms, and the status of extracranial disease. 

Radiation therapy generally is considered to be the treatment of choice for most patients. Exceptions to this include patients with prior radiation to the treatment site and patients with inherently radioresistant tumors (e.g., melanoma and renal cell carcinoma). The radiation field should include two vertebral bodies above and below the involved area. 

In phase I clinical trials 47 patients, all of whom had previously failed standard treatments for solid tumors, received the drug in the UK, Italy, and Switzerland on three different schedules.123,124 Dose-limiting toxicities have been defined as bone marrow depression and diarrhea. The latter is treatable with loperamide. Signs of biological activity were seen. Notably one patient with metastatic pancreatic cancer showed a partial response (for 4 months) and two further patients, one with metastatic melanoma and one with bronchoalveolar carcinoma, also showed partial responses. In a phase I trial in combination with 5-FU, a partial response in breast cancer was observed.125 Furthermore, a reduction in tumor marker levels was observed in two patients, one with ovarian cancer, and one with colon cancer. Phase II studies have shown partial responses in cisplatin-resistant ovarian and nonsmall-cell lung cancer.126,127 The indications are that the profile of clinical activity is different and complementary to the mononuclear platinum agents. 

S. Kashiwagi, Y. Izumi, T. Gohongi, Z.N. Demou, L. Xu, P.L. Huang, D.G. Buerk, L.L. Munn, R K. Jain, and D. Fukumura, NO mediates mural cell recruitment and vessel morphogenesis in murine melanomas and tissue-engineered blood vessels. J. Clin. Invest. 115, 1816-1827 (2005). 

Experiments conducted in the early 1980s showed that lymphocytes incubated in vitro with IL-2 could subsequently kill a range of cultured cancer cell lines, including melanoma and colon cancer cells. These latter cancers do not respond well to conventional therapies. Subsequent investigations showed that cancer cell destruction was mediated by IL-2-stimulated NK cells (i.e. LAK cells). Similar responses were seen in animal models upon administration of LAK cells activated in vitro using IL-2. 

Dibutyltin glycylglycinate 44 (where R = butyl) is the most active organotin complex against p388 leukemia, but is inactive against L1210 leukemia, B16 melanoma, and Lewis lung carcinoma in mice (212). 

K2. Keren, Z., and LeGrue, S. J., Identification of cell surface cathepsin B-like activity on murine melanomas and fibrosarcomas Modulation by butanol extraction. Cancer Res. 48, 1416-1421 (1988). 

Ultraviolet radiation Invisible rays that are part of the energy that comes from the sun. UV radiation can damage the skin and cause melanoma and other types of skin cancer. UV radiation that reaches the earth s surface is made up of two types of rays, called UVA and UVB rays. UVB rays are more likely than UVA rays to cause sunburn, but UVA rays pass deeper into the skin. Scientists have long thought that UVB radiation can cause melanoma and other types of skin cancer. They now think that UVA radiation also may add to skin damage that can lead to skin cancer and cause premature aging. For this reason, skin specialists recommend that people use sunscreens that reflect, absorb, or scatter both kinds of UV radiation. [NIH]... 

This digestion, isolation, and storage approach has been successfully applied to a wide range of tumor and normal tissues. Tumor tissues include both primary and metastatic tumors of the more common types, such as colon, lung, and ovarian tumors, melanomas, and sarcomas, and rare tumors, such as schwannoma. Normal cell populations include lung, ovary, colon, heart, liver, kidney, and blood. 

As might be expected from a screen in which the target tumor was a soft tissue sarcoma, those tumors were among the most sensitive to the compound, along with ovarian tumors, mesotheliomas, melanomas, and lung carcinomas. Tumors least sensitive to this compound included pancreatic carcinomas, neuroblastomas, and especially, renal cell carcinomas. As a rule, for the seven classes of compounds identified in the screen, soft tissue sarcomas, ovarian carcinomas, and mesotheliomas were the most sensitive tumor types. 

Proleukin is a recombinant form of IL-2. It is approved for the treatment of malignant melanoma and renal cell cancer. Ontak (denileukin diftitox) is a fusion protein for the treatment of persistent or recurrent T-cell lymphoma. Activated T cells express lL-2 receptors. Ontak has a fragment that binds to the IL-2 receptor while the other part presents a diphtheria toxin to kill the activated T cell. 

IL-2 promotes the growth of B cells for antibody production and induces the release of IFN-yand TNF (see below). It has been approved by the FDA for the treatment of different types of cancer, including metastatic melanoma and metastatic renal carcinoma. Examples of IL-2 for the treatment of malignant melanoma and a protein that targets IL-2 receptor in T-cell lymphoma are given in Exhibit 4.9. 

The two-hit model applies to a number of other inherited neoplasias, including familial breast cancer, familial colon cancer, familial melanoma, and neurofibromatosis. 

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